Unexpected direct dilithiation of a prochiral phosphine borane

Article abstract of DOI:10.1039/c0cc00130a

Dimethylphenylphosphine borane is readily deprotonated at both methyl groups with tBuLi and (R,R)-TMCDA to the corresponding dilithiated Lewis base adduct, featuring an intriguing structural motif with stabilising Li-H interactions.

Full text of DOI:10.1039/c0cc00130a

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Unexpected direct dilithiation of a prochiral phosphine boranew
Viktoria H. Gessner, Stefan Dilsky and Carsten Strohmann*
Received 26th February 2010, Accepted 28th April 2010
First published as an Advance Article on the web 20th May 2010
DOI: 10.1039/c0cc00130a
Dimethylphenylphosphine borane is readily deprotonated at
both methyl groups with tBuLi and (R,R)-TMCDA to the
corresponding dilithiated Lewis base adduct, featuring an
intriguing structural motif with stabilising Li–H interactions.
Dimethylphenylphosphine borane 1 undergoes a direct
a-lithiation of both methyl groups by slowly warming a
mixture of the phosphorous compound with two equivalents
of tBuLi and 1.5 equivalents of the chiral ligand (1R,2R)-
N,N,N0,N0-tetramethylcyclohexane-1,2-diamine [(R,R)-TMCDA]
in n-pentane and diethyl ether from ꢀ78 1C to ꢀ30 1C
(Scheme 2, for further displays see ESIw). Thereby, colourless
crystals of the dilithiated compound 4 [=32ꢁ3 (R,R)-TMCDA]
are formed in 81% isolated yield. The dilithiated phosphine
borane 4 crystallises in the triclinic crystal system, space group
P1.z 4 features an exceptional structural motif consisting of
two molecules of the dilithiated phosphine borane coordinated
by three (R,R)-TMCDA molecules (two molecules in the
asymmetric unit; one is shown in Fig. 1).5 The central unit is
formed by a Li–C–P–eight–membered ring, in the centre of
which a further lithium atom Li2 is located.6 The lithium and
carbon atoms build two Li–C–Li–C–four–membered rings,
which are connected by one common lithium atom. While
Li2 shows four contacts to the lithiated carbon atoms, the
lithium atoms of the central ring (Li1 and Li3) are coordinated
by the nitrogen atoms of the diamine ligand. The fourth
lithium atom, which is located above the Li–C–P–eight–
membered ring, is coordinated by the third (R,R)-TMCDA
molecule and by the hydrogen atoms of the borane units. Such
stabilising Li–H interactions have first been introduced by
K. Wade and coworkers who found an analogous coordination
sphere in TMEDA coordinated lithium tetrahydroborate.7,8
Overall, all lithium atoms possess a coordination number of
four. The Li–C distances [2.213(8) to 2.414(8) A] are longer
than in oligomeric organolithium compounds, the Li–N
distances in the range of fourfold coordinated alkyllithium
bases.5 An eye-catching feature of the structure is the almost
square–planar coordination of Li2 in the centre of the
Li–C–P–eight–membered ring. The angles of 172.4(4) and
166.6(4)1 (between Li2 and the carbon atoms opposite each
other) differ significantly from the typically observed tetra-
hedral angles at lithium as are observed for Li1, Li3 and Li4.
The dilithiation of 1 has also been observed with N,N,N0,N0-
tetramethylethylenediamine (TMEDA) and (ꢀ)-sparteine as
auxiliaries. Due to ligand disorder, crystals obtained from
dilithiated phosphine borane and TMEDA were only of poor
quality. However, the TMEDA coordinated aggregate showed
the same structural motif as 4. Several further phosphine
boranes, sulfides and oxides show also dilithiation in the
presence of diamine ligands like TMEDA, TMCDA or
(ꢀ)-sparteine.9 3 is a rare example of a dilithiated species,
which is prepared by direct deprotonation of two methyl
groups and structurally characterised.4,10,11
Chiral and achiral phosphane ligands have gained huge impact
in transition metal–catalyzed reactions such as in Kumada and
Suzuki cross–coupling reactions, Heck reaction, enolate arylation
and allylation and direct arylation. Especially chiral phosphane
ligands have become of great importance due to their application
in asymmetric synthesis. Prominent representatives of this
class of compounds are BINAP, CHIRAPHOS or DIPAMP,
which even belong to the routinely used ligands in enantio-
selective reactions.1 In recent years, the (ꢀ)-sparteine mediated
asymmetric deprotonation of dimethylphoshine boranes with
organolithium bases has become the method of choice for the
preparation of chiral phosphane ligands.2 Typically, these
asymmetric lithiations are accomplished with an excess of
the lithium base to account for the loss of base due to
decomposition of the solvent or the ligand. However, possible
side reactions of the excessive alkyllithium reagent, like
dilithiations or the formation of aggregates, have never been
considered before (Scheme 1), although there are some examples
of a direct deprotonation of two methyl groups.3 Generally,
such bis-lithiomethyl compounds are only available by metal–
lithium exchange, halide–lithium exchange or reductive
cleavage of carbon–sulfur bonds.4 For the direct deprotonation
elevated temperatures are usually required, which limits the
synthetic potential due to side reactions like the decomposition
of the additive or the solvent. However, for phosphine borane
1 we observe an exceptional facile deprotonation of both
methyl groups which provides high yielding access to interesting
building blocks for transition metal complexes.
Scheme 1 Dilithiation (left) and asymmetric deprotonation of 1.2g,h
Anorganische Chemie, Technische Universitat Dortmund,
¨
Otto-Hahn-Straße 6, 44227 Dortmund, Germany.
E-mail: mail@carsten-strohmann.de; Fax: (+49)755-7062;
Tel: (+49)755-3807
w Electronic supplementary information (ESI) available: Experimental,
spectroscopic, computational details and crystallographic data of the
presented compounds. CCDC 746595 and 746596. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c0cc00130a
The dilithiation of 1 offers access to novel phosphane ligands.
Trapping with tributyltin chloride to detect all lithiated spieces
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Scheme 3 Trapping of the dilithiated phosphine borane 3.
Scheme 2 Dilithiation of dimethylphosphine borane 1.
Fig. 2 Molecular structure of 6 (for bond lengths and angles,
see ESIw).
Lewis base (which was also found to support the dilithiation in
experiment) were performed to evaluate the reaction barriers
of the mono- and dilithiation.13 The geometries of the stationary
points were initially optimized by using the hybrid B3LYP
functional and the 6-31+G(d) basis set.14 To identify transition
state structures, frequency calculations were carried out on
the same level. Monomeric tBuLiꢁTMEDA was chosen as
deprotonation reagent. Such a monomer is reasonable as an
analogue adduct has been observed with (R,R)-TMCDA.15
The calculations (Fig. 3, ESIw) indicate a barrier of only
61 kJ molꢀ1 for the deprotonation of the first methyl group
and a barrier of 92 kJ molꢀ1 for the abstraction of the second
hydrogen, thus confirming the viability of the mono- and
dilithiation at low temperatures. The low barrier of the
monolithiation is in accordance with the possible asymmetric
deprotonation of dimethylphosphine boranes.2 The energy
difference of 31 kJ molꢀ1 between mono- and dilithiation is
sufficiently high for a kinetic control of both reactions depending
on the reaction temperature and the amount of lithium base.
The barrier of the deprotonation of the second methyl
group (92 kJ molꢀ1) is low enough to be overcome at
temperatures below room temperature. As is evident from
the optimised transition state structures (Fig. 3) this low
reaction barrier can be attributed to the coordination of both
lithium atoms by the hydrogen atoms of the borane moiety
thus stabilising the transition states. The optimised transition
states structures feature Li–H interactions (2.04–2.15 A)
comparable to those found in the crystal structure of 4
(Fig. 1). Compared to a transition state without stabilising
Li–H contact (distance greater than 3.80 A) this interaction
leads to a decreased reaction barrier by 12 kJ molꢀ1 and thus is
crucial for the viability of the dilithiation (see ESIw). It is
noteworthy, that this low barrier is required for the preparation
of the dilithiated compound to exclude side reactions such as
Fig. 1 Molecular structure of 4 (some hydrogen atoms are omitted
for clarity). Selected bond lengths (A) and angles (1): C7–Li1
2.213(8),C7–Li2 2.410(8), C8–Li3 2.250(8), C8–Li2 2.269(8),
C15–Li3 2.234(8), C15–Li2 2.414(8), C16–Li1 2.227(8), C16–Li2
2.265(8), Li1–N2 2.161(7), Li1–N1 2.171(7), Li1–Li2 2.557(10),
Li2–Li3 2.570(10), Li3–N4 2.160(8), Li3–N3 2.195(7), Li4–N6
2.150(7), Li4–N5 2.178(7), B1–Li4 2.479(7), B2–Li4 2.509(8),
Li4–H1A 2.17(5), Li4–H1C 1.92(4), Li4–H2C 2.15(5); C8–Li2–C15
108.1(3), C8–Li2–C7 73.0(2), C16–Li2–C8 166.6(4), C16–Li2–C15
73.4(2), C7–Li2–C15 172.4(4).
in the reaction mixture yields the distannylated compound 5 in
74% yield after work-up (Scheme 3).12 Only traces of the
product from monolithiation could be observed. Analogue
reactions with silicon electrophiles lead to transmetallation
processes in the monosilylated product and thus to product
mixtures. Comparable to the monolithiated phosphine borane
2, 3 can also be transferred to dialcohol 6 as crystalline solid by
trapping with benzophenone (Scheme 3, Fig. 2). 5 was
obtained as a crystalline solid after purification by column
chromatography crystallising in the monoclinic crystal system,
space group P21/c. Most interestingly, in the crystal both
hydroxyl functions are arranged to one side of the molecule
pointing in direction to the borane function and thus indicating
a chelating character of the ligand. This might be due to
Hdꢀ–Hd+ interactions between the negatively polarised
borane hydrogen atom and the positively polarised hydroxyl
hydrogen atom (short H–H distances of 1.97(2) and 2.08(2) A).
The unusual readiness of dilithiation of 1 even at temperatures
below ꢀ30 1C prompted us to take a closer glance at the
ongoing processes. Therefore, DFT studies with TMEDA as
ꢂc
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646; (f) C. Scriban and D. S. Glueck, J. Am. Chem. Soc., 2006, 128,
2788; (g) M. J. McGrath and P. O’Brien, J. Am. Chem. Soc., 2005,
127, 16378; (h) D. Stead, P. O’Brien and A. Sanderson, Org. Lett.,
2008, 10, 1409; (i) T. Imamoto, J. Watanabe, Y. Wada,
H. Masuda, H. Yamada, H. Tsurta, S. Matsukawa and
K. Yamaguchi, J. Am. Chem. Soc., 1998, 120, 1635.
3 (a) H. H. Karsch, Chem. Ber., 1996, 129, 483; (b) W.-P. Leung,
K. S. M. Poon, T. C. W. Mak and Z.-Y. Zhang, Organometallics,
1996, 15, 3262; (c) I. Kamps, A. Mix, R. J. F. Berger, B. Neumann,
H.-G. Stammler and N. W. Mitzel, Chem. Commun., 2009, 5558.
4 For review, see: D. Schildbach and C. Strohmann, in The
Chemistry of Organolithium Compounds, ed. Z. Rappoport and
I. Marek, Wiley, Chichester, 2004, pp. 941–996.
5 For reviews, see: (a) V. H. Gessner, C. Daschlein and
¨
C. Strohmann, Chem.–Eur. J., 2009, 15, 3320; (b) T. Stey and
D. Stalke, in The Chemistry of Organolithium Compounds, ed.
Z. Rappoport and I. Marek, Wiley, Chichester, 2004, pp. 47–120.
6 R. E. Cramer, M. A. Bruck and J. W. Gilje, Organometallics, 1986,
5, 1496.
7 D. R. Armstrong, W. Clegg, H. M. Colquhoun, J. A. Daniels,
R. E. Mulvey, I. R. Stephenson and K. Wade, J. Chem. Soc.,
Chem. Commun., 1987, 630.
8 For further reports about Li–H–B interactions see: (a) A. Heine
and D. Stalke, J. Organomet. Chem., 1997, 542, 25; (b) K. Izod,
L. J. Bowman, C. Wills, W. Clegg and R. W. Harrington, Dalton
Trans., 2009, 3340; (c) K. Izod, W. McFarlane, B. V. Tyson,
W. Clegg and R. W. Harrington, Chem. Commun., 2004, 570;
(d) K. Izod, C. Wills, W. Clegg and R. W. Harrington, Organo-
metallics, 2006, 25, 38.
Fig. 3 Optimised transition state structures of the mono- and
dilithiation of 1 with tBuLiꢁTMEDA; B3LYP/6-31+G(d).
decomposition reactions of the solvent or the chiral additive.
The deprotonation of the (R,R)-TMCDA ligand for example
showed a barrier of 98 kJ molꢀ1, and lithiation of TMEDA a
barrier of 101 kJ molꢀ1, which are higher than the barrier of
the dilithiation.15 Consequently, the calculations confirm the
observed favoritism of the dilithiation over the decomposition
of the ligand and the solvent and thus explains the possible
direct deprotonation of both methyl groups.
9 V. H. Gessner, Dissertation, Technische Universitat Dortmund,
¨
2009.
10 For dilithiation of aromatic compounds, see: (a) M. Kranz,
H. Dietrich, W. Mahdi, G. Muller, F. Hampel, T. Clark,
¨
In conclusion, we reported on the unexpected direct
dilithiation of the prochiral dimethylphenylphosphine borane
1. X-ray diffraction analysis of the diamine coordinated,
dilithiated product 3 showed an extraordinary structural
motif. Computational studies explain the facile deprotonation
of both methyl groups by the interaction of the lithium atoms
with the hydrogens of the borane moiety. We are currently
evaluating the potential of 3 as dilithiated building block for
different electrophiles and stepwise addition reactions.
We thank the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie (FCI). V.H.G specially thanks
the FCI for the award of a doctoral scholarship.
R. Hakcer, W. Neugebauer, A. J. Kos and P. v. R. Schleyer,
J. Am. Chem. Soc., 1993, 115, 4698; (b) G. Linti, A. Rodid and
H. Pritzkow, Angew. Chem., Int. Ed., 2002, 41, 4503;
(c) A. W. Kleij, H. Kleijn, J. T. B. H. Jastrzebski, W. J. J.
Smeets, A. L. Spek and G. van Koten, Organometallics, 1999,
18, 268; (d) M. Winkler and M. Lutz amd G. Muller, Angew.
¨
Chem., Int. Ed. Engl., 1994, 33, 2279; (e) P. Chadha, J. L. Dutton,
M. J. Sgro and P. J. Ragogna, Organometallics, 2007, 26, 6063;
(f) H. Braunschweig, N. Buggisch, U. Englert, M. Homberger,
T. Kupfer, D. Leusser, M. Lutz and K. Radacki, J. Am. Chem.
Soc., 2007, 129, 4840; (g) C. Strohmann, K. Lehmen, A. Ludwig
and D. Schildbach, Organometallics, 2001, 20, 4138.
11 For dilithiation of saturated compounds, see: (a) J. F. K. Muller,
¨
M. Neuburger and B. Springer, Angew. Chem., Int. Ed., 1999, 38,
92; (b) J. F. K. Muller, M. Neuburger and B. Springer, Angew.
¨
References
Chem., Int. Ed., 1999, 38, 3549; (c) A. Kasani, R. P. K. Babu,
R. McDonald and R. G. Cavell, Angew. Chem., Int. Ed., 1999, 38,
1483; (d) C. M. Ong and D. W. Stephan, J. Am. Chem. Soc., 1999,
121, 2939; (e) C. Strohmann, Angew. Chem., Int. Ed. Engl., 1996,
35, 528; (f) C. Strohmann, K. Lehmen and S. Dilsky, J. Am. Chem.
z Crystal data for the dilithiated phosphine borane 4:
C46H90B2Li4N6P2, M = 838.56 g molꢀ1, triclinic, P1, a = 13.792(4)
A, b = 14.275(5) A, c = 16.271(4) A, a = 76.327(7)1, b = 66.351(7)1,
g = 65.941(5)1, V = 2669.3(15) A3, T = 173(2) K, Z = 2, 56322
reflections measured, 18625 independent reflections (Rint = 0.0522).
R1 = 0.0603 [reflections with I > 2s(I)], wR2 = 0.1555 (all data).
CCDC 746595; Crystal data for dialcohol 8: C34H34BO2P,
M = 516.39 g molꢀ1, monoclinic, P21/c, a = 11.9867(15) A,
Soc., 2006, 128, 8102; (g) C. Strohmann, S. Ludtke and O. Ulbrich,
¨
Organometallics, 2000, 19, 4223; C. Strohmann and B. C. Abele,
Angew. Chem., 1996, 108, 2514; (h) C. Strohmann, S. Ludtke and
E. Wack, Chem. Ber., 1996, 129, 799.
¨
12 Also the one-step coupling reaction of 3 with CuCl2 to a six-
membered phosphorous cycle is possible (see ESI): This compound
has been described via a stepwise deprotonation: Y. Morisaki,
H. Imoto, Y. Ouchi, Y. Nagata and Y. Chujo, Org. Lett., 2008, 10,
1489.
b
= 13.8915(11) A, c = 17.6964(16) A, b = 109.362(12)1,
V = 2780.0(5) A3, T = 173(2) K, Z = 4, 17640 reflections measured,
5408 independent reflections (Rint = 0.0358). R1 = 0.0371 [reflections
with I > 2s(I)], wR2 = 0.0727 (all data). CCDC 746596.
13 M. J. Frisch et al., Gaussian03 (Revision D.01), see ESI.
14 A. D. Becke, J. Chem. Phys., 1993, 98, 5648.
1 (a) H. B. Kagan and T. P. Dang, J. Am. Chem. Soc., 1972, 94,
6429; (b) W. S. Knowles, Acc. Chem. Res., 1983, 16, 106;
(c) M. D. Fryzuk and B. Bosnich, J. Am. Chem. Soc., 1978, 100,
5491; (d) R. Noyori and H. Takaya, Acc. Chem. Res., 1990, 23,
345.
2 For examples, see: (a) A. R. Muci, K. R. Campos and D. A. Evans,
J. Am. Chem. Soc., 1995, 117, 9075; (b) K. Nagata, S. Matsukawa
and T. Imamoto, J. Org. Chem., 2000, 65, 4185; (c) C. Genet,
S. J. Canipa, P. O’Brien and S. Taylor, J. Am. Chem. Soc., 2006,
128, 9336; (d) K. M. Pietrusiewicz and M. Zablocka, Chem. Rev.,
1994, 94, 1375; (e) D. Liu and X. Zhang, Eur. J. Org. Chem., 2005,
15 (a) C. Strohmann, V. H. Gessner and A. Damme, Chem. Commun.,
2008, 3381; (b) C. Strohmann and V. H. Gessner, Angew. Chem.,
Int. Ed., 2007, 46, 4566; (c) C. Strohmann and V. H. Gessner,
Angew. Chem., Int. Ed., 2007, 46, 8281; (d) C. Strohmann and
V. H. Gessner, J. Am. Chem. Soc., 2007, 129, 8952;
(e) C. Strohmann and V. H. Gessner, J. Am. Chem. Soc., 2008,
130, 11719; (f) V. H. Gessner and C. Strohmann, J. Am. Chem.
Soc., 2008, 130, 14412; (g) V. H. Gessner and C. Strohmann,
Organometallics, 2010, 29, 1858.
ꢂc
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Chem. Commun., 2010, 46, 4719–4721 | 4721